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Abstract. Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by expansion of the fibroblast and myofibroblast population and extracellular matrix deposition. Although the pathogenic mechanisms of IPF remain to be fully elucidated, there is emerging evidence that fibroblasts and myofibroblasts may be derived partially from alveolar epithelial cells by epithelial-mesenchymal transition (EMT). In the present study, A549 cells were treated with different concentrations of Wnt1 and the results indicated that the mRNA and protein expression levels of vimentin, α-smooth muscle actin (α-SMA) and collagen Ⅰ gradully increased and those of E-cadherin gradully decreased in a concentration-dependent manner. Furthermore, the A549 cells were transfected with β-catenin plasmid cells, revealing phenotypic changes in the cells from a pebble to a fusiform shape. The mRNA and protein expression levels of of vimentin, α-SMA and collagen Ⅰ increased significantly, whereas those of E-cadherin decreased significantly. The present study examined the roles of alveolar epithelial cell injury and profibrogenic cytokine release in EMT and their association with the Wnt/β-catenin signaling pathway in a mouse model of bleomycin-induced pulmonary fibrosis. Bronchoalveolar fluid was obtained 7 days after treatment with bleomycin and the A549 cells were incubated for 48 h. An increase in the expression levels of the mesenchymal markers, α-SMA, vimentin and collagen Ⅰ, and a concomitant decrease in the expression of the epithelial marker, E-cadherin were observed. This corresponded with an increased expression of β-catenin. When the A549 cells were infected with a lentivirus expressing β-catenin shRNA, no significant increase was observed in the expression of the mesenchymal cell markers and the expression of E-cadherin did not decrease. These findings demonstrated that activation of the Wnt signaling pathway was capable of inducing an EMT program in the lung epithelial cells through β-catenin and that injured alveolar epithelium activated the Wnt/β-catenin signaling pathway, thereby inducing the expansion of the fibroblast/myofibroblast population through EMT. These results suggested that β-catenin was involved in the formation of lung fibrosis and may provide a theoretical basis for the treatment of IPF. IntroductionIdiopathic pulmonary fibrosis (IPF) is a progressive disorder of unknown etiology, which has limited response to currently available therapies and a mean survival expectancy of 3-5 years (1). Over the last few years, there has been increasing evidence that IPF may result from acute lung injury targeting alveolar epithelial cells and consequent aberrant wound healing leading to the formation of fibroblastic foci, which are considered to be the active sites of fibrogenesis (2). Fibroblastic foci are composed mainly of fibroblasts and myofibroblasts, which promote excessive deposition of extracellular connective matrix in the pulmonary interstitium during the pathogenesis and progression of pulmonary fibrosis, w...

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Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.

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